DESCRIPTION: (Applicant's Description) This application requests funds to support an embyro manipulation core resource that will assist the efforts of Stanford investigators who would otherwise not have access to this technology. The facility will serve as a resource for the planning, conduct, and interpretation of experiments that involve embyro manipulation techniques. Highly skilled technical personnel supported by these funds will provide microinjection services for creation of transgenic, gene-targeted mice and chimeric mice. The facility will also serve as a repository for fully characterized, totipotent embryonic stem cells for use in gene targeting experiments. Transfections for creation of knock-out and knock-in mutant ES cells will be performed. Mouse lines established by the facility or obtained from other investigators will be maintained, standardized, and disseminated to investigators on an ad hoc basis. For long-term preservation of mouse lines, the facility will provide sperm freezing services. The facility and its scientific advisory staff will serve as a valuable resource for the creation and study of genetically modified mouse strains that will contribute to our understanding of cancer pathogenesis and the molecular mechanisms regulating cellular growth, development and differentiation.